Soluble immunoregulatory factors produced by T lymphocytes have been proposed to explain the phenomena of antigenic competition and immunologic tolerance. To examine this hypothesis, we propose to use an in vivo culture technique: Millipore diffusion chambers will be implanted into mice which have been made tolerant to human gamma globulin (HGG); the diffusion chambers will contain normal syngeneic spleen cells and aggregated HGG or HGG coupled to erythrocytes. The ability of the chamber-enclosed spleen cells to respond to HGG will be tested and the results interpreted in the light of the hypothesis that a soluble, antigen-specific factor may mediate tolerance and so be capable of affecting the chamber-enclosed cells. Similarly, Millipore diffusion chambers containing syngeneic spleen cells and sheep red cells will be implanted in mice undergoing a primary or secondary response to horse red cells which will have been injected intravenously into the chamber hosts. The ability of the chamber-enclosed spleens to mount a primary antibody response against the sheep red cells in mice which are simultaneously undergoing a vigorous immune response to a heterologous antigen will be interpreted in light of the hypothesis that an antigen-non-specific factor mediates the phenomenon of antigenic competition and so should be capable of affecting the chamber-enclosed cells. BIBLIOGRAPHIC REFERENCES: Susan Zolla-Pazner, F. Falkenberg and D. Naor. Is Tolerance an Active or Defective State? Transp. Proc. 7, 381, 1975. Susan Zolla-Pazner and Catherine Koehne. Humoral Mediator of Antigenic Competition Demonstrated in vivo (Abstr.), Fed. Proc., in press.